Philippine E-Journals

Probing the Role of Different Membrane Repair Mechanisms During Necroptotic Cell Death

Rafael A. Espirutu | Uris Ros | Ana J. Garcia-saez

 

Abstract:

Necroptosis is a caspase-independent form of regulated cell death involved in numerous pathophysiological conditions. This mechanism of cell death is inherently immunogenic due to the release of damage-associated molecular patterns upon plasma membrane rupture. During the execution of necroptosis, the cell activates various counterbalancing repair mechanisms that serve to delay cell death and allow proper cell-to-cell communication to occur. Here, we show that CHMP4B, an ESCRT-III component previously implicated in membrane repair, is activated, and forms punctae concomitant with an increase in cytosolic Ca2+ concentration. Previous data showed that damaged membranes were shed during necroptosis, which we similarly observed but only in a very small proportion of cells. Instead, most of the CHMP4B punctae appeared intracellular in nature, suggesting the possible involvement of other pathways in membrane repair. Shedding light on how these repair mechanisms work during necroptosis will be important towards understanding the potential means by which we can control this type of cell death, and possibly exploit it for some therapeutic benefit.